Digoxin with Quinidine Interaction Details

Brand Names Associated with Digoxin

Brand Names Associated with Quinidine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Jan 08, 2024

Interaction Effect

Increased digoxin plasma concentrations

Interaction Summary

Concurrent quinidine and digoxin increased digoxin levels by 0.5 nanogram/mL (0.64 nanomol/L) or greater in 90% of patients and increased serum digoxin concentrations by 100% . Concomitant quinidine and IV digoxin increased digoxin AUC by 54% to 83%. Measure digoxin levels prior to concurrent use. Reduce the digoxin dose by about 30% to 50% or modify the dosing frequency. Continue monitoring digoxin plasma levels .

Severity

Major

Onset

Delayed

Evidence

Established

How To Manage Interaction

The concomitant administration of quinidine and digoxin may increase digoxin exposure or serum digoxin concentrations . Measure digoxin concentrations prior to initiation of concurrent use. Reduce the digoxin dose by approximately 30% to 50% or modify the dosing frequency. Continue monitoring digoxin plasma concentration levels .

Mechanism Of Interaction

Inhibition of P-glycoprotein by quinidine

Literature Reports

A) In pharmacokinetic studies, the concomitant administration of quinidine and digoxin increased serum digoxin concentrations by 100% . Concomitant administration of quinidine and IV digoxin increased digoxin AUC by 54% to 83% .

B) The effect of digoxin on the pharmacokinetics of quinidine was studied in 6 healthy volunteers. Alterations were found in the pharmacokinetics of quinidine, including significantly reduced elimination and increased half-life. The AUC of quinidine was elevated, but not significantly. Digoxin had a significantly increased AUC resulting from reduced renal and total digoxin clearance .

C) Serum digoxin levels were observed in 27 patients on steady-state doses of digoxin, who were not taking any other antiarrhythmic drugs before or during quinidine therapy . In 25 patients, the serum digoxin level rose significantly during quinidine therapy from a mean level of 1.4 nanogram/mL (ng/mL; 1.79 nanomol/L) to 3.2 ng/mL (4.1 nanomol/L), in spite of a reduction in the mean dose of digoxin from 0.31 mg to 0.25 mg. Anorexia, nausea, and vomiting developed in 16 patients on combination therapy, and disappeared in 10 patients when the digoxin dose was lowered or held. Four patients with prior ventricular arrhythmias experienced a worsened arrhythmia within 5 days after quinidine was initiated. Of 13 patients without prior ventricular premature beats, 3 developed this symptom in the same time period. One of those patients manifested ventricular fibrillation, one had asystole, and there was one sudden death. Similar but lesser effects have also been reported with digitoxin .

D) Alteration in renal clearance may be due to decreased renal-tubular secretion of digoxin . An average 42% decrease in biliary clearance of digoxin when co-treated with quinidine was reported . The effect of quinidine digoxin t(1/2) ranges from no significant change  to a significant increase .

E) The literature is conflicting regarding the clinical significance of the increase in serum digoxin levels. Although digitalis toxicity has been reported, several studies have reported a decrease in myocardial performance in the presence of elevated serum digoxin concentration during quinidine therapy . Research suggests that the decrease in tissue binding may decrease the efficacy of digoxin despite increased levels, making dosage adjustments of digoxin unnecessary during combined treatment . Routine downward adjustments of the digoxin dose by 50% have been recommended by others whenever quinidine is added to the regimen .

Digoxin Overview

• Digoxin is used to treat heart failure and abnormal heart rhythms (arrhythmias). It helps the heart work better and it helps control your heart rate.

Quinidine Overview

• Quinidine is used to treat certain types of irregular heartbeats. Quinidine is in a class of medications called antiarrhythmic medications. It works by making your heart more resistant to abnormal activity.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.